NS1
MCID: NNN008
MIFTS: 76

Noonan Syndrome 1 (NS1)

Categories: Cardiovascular diseases, Ear diseases, Endocrine diseases, Eye diseases, Fetal diseases, Genetic diseases, Nephrological diseases, Neuronal diseases, Rare diseases, Reproductive diseases, Skin diseases

Aliases & Classifications for Noonan Syndrome 1

MalaCards integrated aliases for Noonan Syndrome 1:

Name: Noonan Syndrome 1 57 12 20 72 29 13 6 15
Noonan Syndrome 57 12 73 25 20 43 58 72 36 29 54 6 44 15 70
Female Pseudo-Turner Syndrome 57 20 43 72
Male Turner Syndrome 57 20 43 72
Turner Phenotype with Normal Karyotype 57 43 72
Ns1 57 12 72
Noonan Syndrome with Pigmented Villonodular Synovitis 72 6
Pseudo-Ullrich-Turner Syndrome 20 43
Ullrich-Noonan Syndrome 20 43
Noonan-Ehmke Syndrome 20 43
Noonan Syndrome-Like Disorder with Multiple Giant Cell Lesions 72
Noonan-Like/multiple Giant Cell Lesion Syndrome 72
Turner Syndrome in Female with X Chromosome 43
Turner's Phenotype, Karyotype Normal 12
Pterygium Colli Syndrome 72
Familial Turner Syndrome 43
Syndrome, Noonan, Type 1 39
Turner Syndrome, Male 70
Turner-Like Syndrome 43
Noonan's Syndrome 43
Syndrome, Noonan 39
Ns 43

Characteristics:

Orphanet epidemiological data:

58
noonan syndrome
Inheritance: Autosomal dominant; Prevalence: 6-9/10000 (Europe); Age of onset: Neonatal; Age of death: normal life expectancy;

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal dominant

Miscellaneous:
genetic heterogeneity
allelic to leopard syndrome


HPO:

31
noonan syndrome 1:
Inheritance autosomal dominant inheritance


GeneReviews:

25
Penetrance Penetrance of ns is difficult to determine because of ascertainment bias and variable expressivity with frequent subtlety of features. many affected adults are diagnosed only after the birth of a more obviously affected infant.

Classifications:

Orphanet: 58  
Rare neurological diseases
Rare eye diseases
Rare circulatory system diseases
Rare cardiac malformations
Rare renal diseases
Rare infertility disorders
Rare skin diseases
Rare endocrine diseases
Developmental anomalies during embryogenesis


Summaries for Noonan Syndrome 1

MedlinePlus Genetics : 43 Noonan syndrome is a condition that affects many areas of the body. It is characterized by mildly unusual facial features, short stature, heart defects, bleeding problems, skeletal malformations, and many other signs and symptoms.People with Noonan syndrome have distinctive facial features such as a deep groove in the area between the nose and mouth (philtrum), widely spaced eyes that are usually pale blue or blue-green in color, and low-set ears that are rotated backward. Affected individuals may have a high arch in the roof of the mouth (high-arched palate), poor teeth alignment, and a small lower jaw (micrognathia). Many children with Noonan syndrome have a short neck, and both children and adults may have excess neck skin (also called webbing) and a low hairline at the back of the neck.Between 50 and 70 percent of individuals with Noonan syndrome have short stature. At birth, they are usually a normal length and weight, but growth slows over time. Abnormal levels of growth hormone, a protein that is necessary for the normal growth of the body's bones and tissues, may contribute to the slow growth.Individuals with Noonan syndrome often have either a sunken chest (pectus excavatum) or a protruding chest (pectus carinatum). Some affected people may also have an abnormal side-to-side curvature of the spine (scoliosis).Most people with Noonan syndrome have some form of critical congenital heart disease. The most common heart defect in these individuals is a narrowing of the valve that controls blood flow from the heart to the lungs (pulmonary valve stenosis). Some have hypertrophic cardiomyopathy, which enlarges and weakens the heart muscle.A variety of bleeding disorders have been associated with Noonan syndrome. Some affected individuals have excessive bruising, nosebleeds, or prolonged bleeding following injury or surgery. Rarely, women with Noonan syndrome who have a bleeding disorder have excessive bleeding during menstruation (menorrhagia) or childbirth.Adolescent males with Noonan syndrome typically experience delayed puberty. They go through puberty starting at age 13 or 14 and have a reduced pubertal growth spurt that results in shortened stature. Most males with Noonan syndrome have undescended testes (cryptorchidism), which may contribute to infertility (inability to father a child) later in life. Females with Noonan syndrome can experience delayed puberty but most have normal puberty and fertility.Noonan syndrome can cause a variety of other signs and symptoms. Most children diagnosed with Noonan syndrome have normal intelligence, but a few have special educational needs, and some have intellectual disability. Some affected individuals have vision or hearing problems. Affected infants may have feeding problems, which typically get better by age 1 or 2 years. Infants with Noonan syndrome may be born with puffy hands and feet caused by a buildup of fluid (lymphedema), which can go away on its own. Older individuals can also develop lymphedema, usually in the ankles and lower legs.Some people with Noonan syndrome develop cancer, particularly those involving the blood-forming cells (leukemia). It has been estimated that children with Noonan syndrome have an eightfold increased risk of developing leukemia or other cancers over age-matched peers.Noonan syndrome is one of a group of related conditions, collectively known as RASopathies. These conditions all have similar signs and symptoms and are caused by changes in the same cell signaling pathway. In addition to Noonan syndrome, the RASopathies include cardiofaciocutaneous syndrome, Costello syndrome, neurofibromatosis type 1, Legius syndrome, and Noonan syndrome with multiple lentigines.

MalaCards based summary : Noonan Syndrome 1, also known as noonan syndrome, is related to noonan syndrome with multiple lentigines and neurofibromatosis-noonan syndrome. An important gene associated with Noonan Syndrome 1 is PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11), and among its related pathways/superpathways are Ras signaling pathway and MAPK signaling pathway. The drugs Simvastatin and Hormone Antagonists have been mentioned in the context of this disorder. Affiliated tissues include heart, eye and myeloid, and related phenotypes are ptosis and dysarthria

Disease Ontology : 12 A RASopathy that is characterized by mildly unusual facial features, short stature, heart defects, bleeding problems, skeletal malformations, and many other signs and symptoms.

GARD : 20 Noonan syndrome is a genetic disorder that causes abnormal development of multiple parts of the body. Features of Noonan syndrome may include a distinctive facial appearance, short stature, a broad or webbed neck, congenital heart defects, bleeding problems, problems with bone structure (skeletal malformations), and developmental delay. Noonan syndrome may be caused by a mutation in any of several genes, and can be classified into subtypes based on the responsible gene. It is typically inherited in an autosomal dominant manner, but many cases are due to a new mutation and are not inherited from either parent. Treatment depends on the symptoms present in each person. Noonan syndrome belongs to a group of related conditions called the RASopathies. These conditions have some overlapping features and are all caused by genetic changes that disrupt the body's RAS pathway, affecting growth and development. Other conditions in this group include: neurofibromatosis type 1 LEOPARD syndrome, also called Noonan syndrome with multiple lentigines Costello syndrome cardiofaciocutaneous syndrome Legius syndrome capillary malformation-arteriovenous malformation syndrome

OMIM® : 57 Noonan syndrome (NS) is an autosomal dominant disorder characterized by short stature, facial dysmorphism, and a wide spectrum of congenital heart defects. The distinctive facial features consist of a broad forehead, hypertelorism, downslanting palpebral fissures, a high-arched palate, and low-set, posteriorly rotated ears. Cardiac involvement is present in up to 90% of patients. Pulmonic stenosis and hypertrophic cardiomyopathy are the most common forms of cardiac disease, but a variety of other lesions are also observed. Additional relatively frequent features include multiple skeletal defects (chest and spine deformities), webbed neck, mental retardation, cryptorchidism, and bleeding diathesis (summary by Tartaglia et al., 2002). (163950) (Updated 05-Apr-2021)

KEGG : 36 Noonan syndrome (NS) is an autosomal dominant disorder characterised by short stature, craniofacial dysmorphism, congenital cardiac defects, cryptorchidism in men, coagulation defects, and neurocognitive delay. In addition, individuals with NS have an increased risk of developing cancer. NS is caused by germline mutations in genes that encode components or regulators of the Ras/MAPK pathway. Heterozygous, pathogenic variants in 9 known genes account for approximately 80% of cases. The most common gene associated with NS is PTPN11, which accounts for approximately 50% of all cases.

UniProtKB/Swiss-Prot : 72 Noonan syndrome 1: A form of Noonan syndrome, a disease characterized by short stature, facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears, and a high incidence of congenital heart defects and hypertrophic cardiomyopathy. Other features can include a short neck with webbing or redundancy of skin, deafness, motor delay, variable intellectual deficits, multiple skeletal defects, cryptorchidism, and bleeding diathesis. Individuals with Noonan syndrome are at risk of juvenile myelomonocytic leukemia, a myeloproliferative disorder characterized by excessive production of myelomonocytic cells. Some patients with NS1 develop multiple giant cell lesions of the jaw or other bony or soft tissues, which are classified as pigmented villonodular synovitis (PVNS) when occurring in the jaw or joints.

Wikipedia : 73 Noonan syndrome (NS) is a genetic disorder that may present with mildly unusual facial features, short... more...

GeneReviews: NBK1124

Related Diseases for Noonan Syndrome 1

Diseases in the Noonan Syndrome 1 family:

Noonan Syndrome 2 Noonan Syndrome 3
Noonan Syndrome 4 Noonan Syndrome 5
Noonan Syndrome 6 Noonan Syndrome 7
Noonan Syndrome 8 Noonan Syndrome 9
Noonan Syndrome 10 Noonan Syndrome 11
Noonan Syndrome 12 Noonan Syndrome 13

Diseases related to Noonan Syndrome 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 682)
# Related Disease Score Top Affiliating Genes
1 noonan syndrome with multiple lentigines 34.3 SOS2 SOS1 SHOC2 RASA2 RAF1 PTPN11
2 neurofibromatosis-noonan syndrome 34.1 SOS2 SOS1 SHOC2 PTPN11 PPP1CB MAP2K1
3 pseudo-turner syndrome 33.8 SOS2 SOS1 SHOC2 RRAS2 RIT1 RAF1
4 noonan syndrome-like disorder with loose anagen hair 33.8 SOS2 SOS1 SHOC2 PTPN11 PPP1CB MAP2K1
5 noonan syndrome-like disorder with loose anagen hair 2 33.7 SOS2 SOS1 SHOC2 PTPN11 PPP1CB MAP2K1
6 noonan syndrome-like disorder with loose anagen hair 1 33.6 SHOC2 PTPN11 KRAS HRAS
7 costello syndrome 33.2 SOS2 SOS1 SHOC2 RASA2 PTPN11 MAP2K1
8 leopard syndrome 1 33.2 RAF1 PTPN11 BRAF
9 rasopathy 33.2 SOS2 SOS1 SHOC2 RRAS2 RIT1 RASA2
10 cardiofaciocutaneous syndrome 1 33.0 SOS2 SOS1 SHOC2 RIT1 RASA2 RAF1
11 noonan syndrome and noonan-related syndrome 33.0 SOS1 RAF1 PTPN11 BRAF
12 leopard syndrome 2 32.9 RAF1 PTPN11
13 hypertrophic cardiomyopathy 32.7 SOS2 SOS1 SHOC2 RIT1 RAF1 PTPN11
14 noonan syndrome 3 32.7 SOS1 SHOC2 RAF1 PTPN11 LRRC56 KRAS
15 juvenile myelomonocytic leukemia 32.6 SOS2 SOS1 RRAS2 RIT1 RASA2 RAF1
16 pulmonary valve stenosis 32.2 SOS2 SOS1 SHOC2 RASA2 PTPN11 MAP2K1
17 neurofibromatosis 32.2 SOS1 RASA2 PTPN11 KRAS HRAS
18 lentigines 32.1 RAF1 PTPN11 BRAF
19 noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia 32.0 PTPN11 CBL
20 leukemia 31.9 RAF1 PTPN11 NRAS KRAS HRAS CBL
21 neurofibromatosis, type i 31.9 SOS1 RASA2 RAF1 PTPN11 NRAS MAP2K1
22 atrial heart septal defect 31.8 SOS1 SHOC2 PTPN11 LZTR1
23 heart septal defect 31.8 SOS1 SHOC2 PTPN11
24 rhabdomyosarcoma 31.7 SOS1 PTPN11 NRAS MAP2K1 LRRC56 KRAS
25 leukemia, acute myeloid 31.5 PTPN11 NRAS MAP2K1 LRRC56 KRAS HRAS
26 myeloid leukemia 31.5 RAF1 PTPN11 NRAS MAP2K1 KRAS HRAS
27 pilocytic astrocytoma 31.4 SOS1 RAF1 PTPN11 NRAS KRAS HRAS
28 keratosis pilaris atrophicans faciei 31.2 SOS1 PTPN11 MAP2K1
29 embryonal rhabdomyosarcoma 31.1 SOS1 PTPN11 KRAS HRAS
30 patent ductus arteriosus 1 31.1 SOS1 SHOC2 PTPN11
31 lung cancer susceptibility 3 31.0 SOS1 RAF1 PTPN11 NRAS MAP2K1 LRRC56
32 villonodular synovitis 31.0 SOS1 PTPN11
33 chronic myelomonocytic leukemia 31.0 PTPN11 NRAS KRAS CBL
34 arteriovenous malformation 30.9 MAP2K1 LRRC56 KRAS HRAS
35 leukemia, chronic lymphocytic 30.8 PTPN11 NRAS LRRC56 KRAS HRAS BRAF
36 myelodysplastic syndrome 30.8 PTPN11 NRAS LRRC56 KRAS HRAS CBL
37 arteriovenous malformations of the brain 30.8 RASA2 KRAS BRAF
38 ras-associated autoimmune leukoproliferative disorder 30.7 NRAS KRAS HRAS
39 pilomyxoid astrocytoma 30.7 RAF1 KRAS BRAF
40 lynch syndrome 30.6 NRAS KRAS HRAS BRAF
41 noonan syndrome 4 11.7
42 noonan syndrome 6 11.7
43 noonan syndrome 5 11.7
44 noonan syndrome 7 11.7
45 multiple pterygium syndrome, escobar variant 11.5
46 short-rib thoracic dysplasia 3 with or without polydactyly 11.4
47 leopard syndrome 3 11.3
48 legius syndrome 11.1
49 medulloblastoma 11.1
50 hypertelorism 11.1

Graphical network of the top 20 diseases related to Noonan Syndrome 1:



Diseases related to Noonan Syndrome 1

Symptoms & Phenotypes for Noonan Syndrome 1

Human phenotypes related to Noonan Syndrome 1:

58 31 (show top 50) (show all 89)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 ptosis 58 31 very rare (1%) Very frequent (99-80%) HP:0000508
2 dysarthria 58 31 hallmark (90%) Very frequent (99-80%) HP:0001260
3 high palate 58 31 hallmark (90%) Very frequent (99-80%) HP:0000218
4 muscle weakness 58 31 hallmark (90%) Very frequent (99-80%) HP:0001324
5 hypertelorism 58 31 very rare (1%) Very frequent (99-80%) HP:0000316
6 pectus carinatum 58 31 hallmark (90%) Very frequent (99-80%) HP:0000768
7 short stature 58 31 very rare (1%) Very frequent (99-80%) HP:0004322
8 thick lower lip vermilion 58 31 hallmark (90%) Very frequent (99-80%) HP:0000179
9 aplasia/hypoplasia of the abdominal wall musculature 58 31 hallmark (90%) Very frequent (99-80%) HP:0010318
10 enlarged thorax 58 31 hallmark (90%) Very frequent (99-80%) HP:0100625
11 wide intermamillary distance 58 31 hallmark (90%) Very frequent (99-80%) HP:0006610
12 micrognathia 58 31 hallmark (90%) Very frequent (99-80%) HP:0000347
13 webbed neck 58 31 very rare (1%) Very frequent (99-80%) HP:0000465
14 thickened nuchal skin fold 58 31 hallmark (90%) Very frequent (99-80%) HP:0000474
15 cystic hygroma 58 31 hallmark (90%) Very frequent (99-80%) HP:0000476
16 pectus excavatum 58 31 hallmark (90%) Very frequent (99-80%) HP:0000767
17 downslanted palpebral fissures 58 31 very rare (1%) Very frequent (99-80%) HP:0000494
18 low-set, posteriorly rotated ears 58 31 hallmark (90%) Very frequent (99-80%) HP:0000368
19 joint hyperflexibility 58 31 hallmark (90%) Very frequent (99-80%) HP:0005692
20 proptosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0000520
21 high forehead 58 31 hallmark (90%) Very frequent (99-80%) HP:0000348
22 midface retrusion 58 31 hallmark (90%) Very frequent (99-80%) HP:0011800
23 triangular face 58 31 hallmark (90%) Very frequent (99-80%) HP:0000325
24 thickened helices 58 31 hallmark (90%) Very frequent (99-80%) HP:0000391
25 pulmonary artery stenosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0004415
26 hypogonadotropic hypogonadism 31 hallmark (90%) HP:0000044
27 scoliosis 58 31 frequent (33%) Frequent (79-30%) HP:0002650
28 hepatomegaly 58 31 frequent (33%) Frequent (79-30%) HP:0002240
29 delayed skeletal maturation 58 31 frequent (33%) Frequent (79-30%) HP:0002750
30 coarse hair 58 31 frequent (33%) Frequent (79-30%) HP:0002208
31 feeding difficulties in infancy 58 31 very rare (1%) Frequent (79-30%) HP:0008872
32 strabismus 58 31 frequent (33%) Frequent (79-30%) HP:0000486
33 cryptorchidism 58 31 very rare (1%) Frequent (79-30%) HP:0000028
34 low posterior hairline 58 31 very rare (1%) Frequent (79-30%) HP:0002162
35 abnormal dermatoglyphics 58 31 frequent (33%) Frequent (79-30%) HP:0007477
36 arrhythmia 58 31 frequent (33%) Frequent (79-30%) HP:0011675
37 abnormal pulmonary valve morphology 58 31 frequent (33%) Frequent (79-30%) HP:0001641
38 abnormal platelet function 58 31 frequent (33%) Frequent (79-30%) HP:0011869
39 abnormal hair quantity 58 31 frequent (33%) Frequent (79-30%) HP:0011362
40 abnormality of the spleen 58 31 frequent (33%) Frequent (79-30%) HP:0001743
41 abnormal bleeding 58 31 frequent (33%) Frequent (79-30%) HP:0001892
42 abnormality of coagulation 58 31 frequent (33%) Frequent (79-30%) HP:0001928
43 hypotonia 31 frequent (33%) HP:0001252
44 nystagmus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000639
45 sensorineural hearing impairment 58 31 occasional (7.5%) Occasional (29-5%) HP:0000407
46 lymphedema 58 31 occasional (7.5%) Occasional (29-5%) HP:0001004
47 melanocytic nevus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000995
48 brachydactyly 58 31 occasional (7.5%) Occasional (29-5%) HP:0001156
49 clinodactyly of the 5th finger 58 31 occasional (7.5%) Occasional (29-5%) HP:0004209
50 radioulnar synostosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002974

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Head And Neck Eyes:
ptosis
hypertelorism
myopia
downslanting palpebral fissures
epicanthal folds
more
Head And Neck Teeth:
dental malocclusion

Genitourinary Internal Genitalia Male:
cryptorchidism
occasional hypogonadism
male infertility (in individuals with bilateral cryptorchidism)

Head And Neck Face:
micrognathia
triangular face (with age)

Growth Other:
failure to thrive in infancy
specific growth curves are available

Laboratory Abnormalities:
thrombocytopenia
partial deficiency of factor xi(c)
partial deficiency of factor xii(c)
partial deficiency of factor xiii(c)

Cardiovascular Vascular:
patent ductus arteriosus
aortic coarctation

Hematology:
amegakaryocytic thrombocytopenia
von willebrand disease
bleeding tendency

Head And Neck Ears:
hearing loss, sensorineural
low-set posteriorly rotated ears

Neurologic Central Nervous System:
articulation difficulties
mental retardation (25%)

Head And Neck Neck:
short neck
webbed neck
cystic hygroma

Muscle Soft Tissue:
lymphedema

Skeletal Limbs:
cubitus valgus
brachydactyly
clinodactyly
blunt fingertips
polyarticular villonodular synovitis (knees, ankles, wrists, elbows - in some patients)

Chest Ribs Sternum Clavicles And Scapulae:
shield chest
pectus carinatum superiorly
pectus excavatum inferiorly

Skin Nails Hair Hair:
low posterior hairline
woolly-like hair

Skeletal Spine:
kyphoscoliosis
vertebral abnormalities

Cardiovascular Heart:
pulmonic stenosis
congenital heart defect
ventricular septal defects
hypertrophic obstructive cardiomyopathy
atrial septal defects

Head And Neck Mouth:
high arched palate
deeply grooved philtrum
high peaks of upper lip vermilion border

Growth Height:
short stature (postnatal onset)

Neoplasia:
malignant schwannoma
multiple giant cell granulomas (bones, joints, soft tissues)

Clinical features from OMIM®:

163950 (Updated 05-Apr-2021)

GenomeRNAi Phenotypes related to Noonan Syndrome 1 according to GeneCards Suite gene sharing:

26 (show top 50) (show all 55)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-100 10.63 SOS1
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-110 10.63 BRAF
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-115 10.63 NRAS
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-116 10.63 CBL
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-118 10.63 PTPN11
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-119 10.63 RASA2
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-120 10.63 RASA2 SOS1
8 Decreased shRNA abundance (Z-score < -2) GR00366-A-121 10.63 PTPN11
9 Decreased shRNA abundance (Z-score < -2) GR00366-A-122 10.63 CBL
10 Decreased shRNA abundance (Z-score < -2) GR00366-A-126 10.63 NRAS
11 Decreased shRNA abundance (Z-score < -2) GR00366-A-138 10.63 PTPN11
12 Decreased shRNA abundance (Z-score < -2) GR00366-A-145 10.63 CBL
13 Decreased shRNA abundance (Z-score < -2) GR00366-A-148 10.63 A2ML1 CBL NRAS
14 Decreased shRNA abundance (Z-score < -2) GR00366-A-149 10.63 RAF1 PTPN11 SOS1
15 Decreased shRNA abundance (Z-score < -2) GR00366-A-153 10.63 A2ML1
16 Decreased shRNA abundance (Z-score < -2) GR00366-A-161 10.63 NRAS RAF1
17 Decreased shRNA abundance (Z-score < -2) GR00366-A-166 10.63 BRAF
18 Decreased shRNA abundance (Z-score < -2) GR00366-A-171 10.63 A2ML1
19 Decreased shRNA abundance (Z-score < -2) GR00366-A-177 10.63 BRAF
20 Decreased shRNA abundance (Z-score < -2) GR00366-A-190 10.63 PTPN11
21 Decreased shRNA abundance (Z-score < -2) GR00366-A-194 10.63 BRAF
22 Decreased shRNA abundance (Z-score < -2) GR00366-A-203 10.63 SOS1
23 Decreased shRNA abundance (Z-score < -2) GR00366-A-204 10.63 A2ML1 NRAS RAF1 RASA2
24 Decreased shRNA abundance (Z-score < -2) GR00366-A-208 10.63 NRAS
25 Decreased shRNA abundance (Z-score < -2) GR00366-A-214 10.63 RASA2
26 Decreased shRNA abundance (Z-score < -2) GR00366-A-28 10.63 NRAS
27 Decreased shRNA abundance (Z-score < -2) GR00366-A-29 10.63 BRAF
28 Decreased shRNA abundance (Z-score < -2) GR00366-A-31 10.63 BRAF
29 Decreased shRNA abundance (Z-score < -2) GR00366-A-32 10.63 BRAF
30 Decreased shRNA abundance (Z-score < -2) GR00366-A-37 10.63 PTPN11
31 Decreased shRNA abundance (Z-score < -2) GR00366-A-40 10.63 CBL
32 Decreased shRNA abundance (Z-score < -2) GR00366-A-43 10.63 CBL
33 Decreased shRNA abundance (Z-score < -2) GR00366-A-47 10.63 PTPN11
34 Decreased shRNA abundance (Z-score < -2) GR00366-A-48 10.63 A2ML1
35 Decreased shRNA abundance (Z-score < -2) GR00366-A-54 10.63 NRAS
36 Decreased shRNA abundance (Z-score < -2) GR00366-A-63 10.63 NRAS
37 Decreased shRNA abundance (Z-score < -2) GR00366-A-65 10.63 SOS1
38 Decreased shRNA abundance (Z-score < -2) GR00366-A-68 10.63 A2ML1
39 Decreased shRNA abundance (Z-score < -2) GR00366-A-72 10.63 BRAF
40 Decreased shRNA abundance (Z-score < -2) GR00366-A-89 10.63 RASA2
41 Decreased shRNA abundance (Z-score < -2) GR00366-A-91 10.63 A2ML1
42 Decreased viability GR00055-A-1 10.02 BRAF CBL HRAS KRAS
43 Decreased viability GR00055-A-2 10.02 BRAF CBL HRAS KRAS
44 Decreased viability GR00055-A-3 10.02 KRAS
45 Decreased viability GR00106-A-0 10.02 KRAS
46 Decreased viability GR00221-A-1 10.02 HRAS KRAS
47 Decreased viability GR00221-A-2 10.02 CBL HRAS KRAS
48 Decreased viability GR00221-A-3 10.02 CBL HRAS
49 Decreased viability GR00221-A-4 10.02 BRAF
50 Decreased viability GR00249-S 10.02 BRAF

MGI Mouse Phenotypes related to Noonan Syndrome 1:

46 (show all 16)
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 10.4 BRAF CBL GJB2 HRAS KRAS LZTR1
2 growth/size/body region MP:0005378 10.32 BRAF CBL GJB2 HRAS KRAS LZTR1
3 craniofacial MP:0005382 10.31 BRAF CBL GJB2 HRAS KRAS LZTR1
4 cellular MP:0005384 10.29 BRAF CBL GJB2 KRAS LZTR1 MAP2K1
5 homeostasis/metabolism MP:0005376 10.28 BRAF CBL GJB2 HRAS KRAS LRRC56
6 mortality/aging MP:0010768 10.24 BRAF CBL GJB2 HRAS KRAS LRRC56
7 embryo MP:0005380 10.16 BRAF GJB2 KRAS MAP2K1 NRAS PTPN11
8 endocrine/exocrine gland MP:0005379 10.15 BRAF CBL HRAS KRAS MAP2K1 NRAS
9 integument MP:0010771 10.14 BRAF CBL GJB2 HRAS KRAS MAP2K1
10 digestive/alimentary MP:0005381 10.13 BRAF HRAS KRAS MAP2K1 NRAS PTPN11
11 hearing/vestibular/ear MP:0005377 10 BRAF CBL GJB2 KRAS MAP2K1 PTPN11
12 muscle MP:0005369 9.92 BRAF CBL HRAS KRAS LZTR1 PTPN11
13 normal MP:0002873 9.85 BRAF GJB2 HRAS KRAS MAP2K1 NRAS
14 neoplasm MP:0002006 9.8 BRAF HRAS KRAS MAP2K1 NRAS PTPN11
15 skeleton MP:0005390 9.7 BRAF CBL GJB2 HRAS KRAS LZTR1
16 vision/eye MP:0005391 9.36 BRAF CBL GJB2 KRAS MAP2K1 NRAS

Drugs & Therapeutics for Noonan Syndrome 1

Drugs for Noonan Syndrome 1 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 12)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Simvastatin Approved Phase 3 79902-63-9 54454
2 Hormone Antagonists Phase 3
3 Hormones Phase 3
4 Hydroxymethylglutaryl-CoA Reductase Inhibitors Phase 3
5 Antimetabolites Phase 3
6 Lipid Regulating Agents Phase 3
7 Anticholesteremic Agents Phase 3
8 Hypolipidemic Agents Phase 3
9
Mecasermin Approved, Investigational Phase 2 68562-41-4
10 insulin Phase 2
11 Mitogens Phase 2
12 Insulin, Globin Zinc Phase 2

Interventional clinical trials:

(show all 14)
# Name Status NCT ID Phase Drugs
1 Genetic Testing of Noonan Subjects Previously Treated With Norditropin® in the GHNOO-1658 Trial Completed NCT01529944 Phase 3 somatropin;somatropin
2 Effect of the Growth Hormone MAXOMAT ® on the Growth of Small Children and Adolescents (<-2 SD) Due to NOONAN's Syndrome Completed NCT00452725 Phase 3 MAXOMAT ®, biosynthetic growth hormone
3 A 52-week, Multi-centre, Randomised, Double-blind, Parallel-group, no Treatment Controlled (Open-label) Trial Investigating the Efficacy and Safety of Two Doses of NN-220 in Short Stature With Noonan Syndrome Completed NCT01927861 Phase 3 somatropin
4 Norditropin Treatment in Subjects With Noonan Syndrome. Effects on Linear Growth and Final Height - Data Collection and Follow-up Visit Completed NCT01529840 Phase 3 somatropin;somatropin
5 Treatment With HMG-COA Reductase Inhibitor (Simvastatin) of Growth and Bone Abnormalities in Children With Noonan Syndrome: A Phase III Randomised, Double Blind, Placebo-controlled Therapeutic Trial Recruiting NCT02713945 Phase 3 Simvastatin;Placebo
6 A Phase 2, Open-Label, Multicenter, Clinical Trial to Evaluate the Pharmacokinetics, Safety and Efficacy of Recombinant Human Insulin-Like Growth Factor-1/Recombinant Human Insulin-Like Growth Factor Binding Protein-3 in Children With Growth Failure Due to Noonan Syndrome Terminated NCT00351221 Phase 2 rhIGF-1/rhIGFBP-3
7 An Open Label Study to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MEK162 in Noonan Syndrome Hypertrophic Cardiomyopathy Withdrawn NCT01556568 Phase 2 MEK162
8 Consequences of Noonan Syndrome/LEOPARD Syndrome Associated Shp2 Mutations on Different Signaling Pathways Activation: Relationship With Hormonal Sensitivity Unknown status NCT02486731
9 Study of Metabolic Modifications in Children With Noonan Syndrome Completed NCT02383316
10 NordiNet® International Outcome Study-Observational Prospective Study on Patients Treated With Norditropin® Completed NCT00960128 somatropin;somatropin
11 Familial Investigations of Childhood Cancer Predisposition Recruiting NCT03050268
12 GROWing Up With Rare GENEtic Syndromes ….When Children With Complex Genetic Syndromes Reach Adult Age Recruiting NCT04463316
13 Investigation Into the Natural History and Metabolic and Molecular Basis of RASopathies. Recruiting NCT04395495
14 Post Marketing Surveillance on Long-term Use With Norditropin® (Short Stature Due to Noonan Syndrome) Active, not recruiting NCT03435627 Somatropin

Search NIH Clinical Center for Noonan Syndrome 1

Cochrane evidence based reviews: noonan syndrome

Genetic Tests for Noonan Syndrome 1

Genetic tests related to Noonan Syndrome 1:

# Genetic test Affiliating Genes
1 Noonan Syndrome 1 29 BRAF MAP2K1 PTPN11
2 Noonan Syndrome 29 MAP2K1 PTPN11

Anatomical Context for Noonan Syndrome 1

MalaCards organs/tissues related to Noonan Syndrome 1:

40
Heart, Eye, Myeloid, Testes, Bone, Brain, Spleen

Publications for Noonan Syndrome 1

Articles related to Noonan Syndrome 1:

(show top 50) (show all 1889)
# Title Authors PMID Year
1
Gain-of-function SOS1 mutations cause a distinctive form of Noonan syndrome. 57 25 61 54 6
17143282 2007
2
Germline gain-of-function mutations in SOS1 cause Noonan syndrome. 25 57 6 54 61
17143285 2007
3
Germline KRAS mutations cause Noonan syndrome. 54 25 57 6 61
16474405 2006
4
Noonan syndrome: relationships between genotype, growth, and growth factors. 61 57 6 25 54
16263833 2006
5
PTPN11 mutations are associated with mild growth hormone resistance in individuals with Noonan syndrome. 61 57 6 25 54
15985475 2005
6
PTPN11 (protein tyrosine phosphatase, nonreceptor type 11) mutations and response to growth hormone therapy in children with Noonan syndrome. 61 54 57 6 25
15956085 2005
7
Protein-tyrosine phosphatase, nonreceptor type 11 mutation analysis and clinical assessment in 45 patients with Noonan syndrome. 61 57 54 25 6
15240615 2004
8
Somatic mutations in PTPN11 in juvenile myelomonocytic leukemia, myelodysplastic syndromes and acute myeloid leukemia. 57 6 25 54 61
12717436 2003
9
PTPN11 mutations in Noonan syndrome: molecular spectrum, genotype-phenotype correlation, and phenotypic heterogeneity. 61 54 57 6 25
11992261 2002
10
Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome. 25 57 6 54 61
11704759 2001
11
Clinical and hematologic findings in Noonan syndrome patients with PTPN11 gene mutations. 61 25 6 57
20954246 2010
12
Neurofibromatosis-Noonan syndrome: molecular evidence of the concurrence of both disorders in a patient. 61 57 6 25
15948193 2005
13
Diversity and functional consequences of germline and somatic PTPN11 mutations in human disease. 61 6 54 57
16358218 2006
14
Clinical variability in a Noonan syndrome family with a new PTPN11 gene mutation. 61 57 54 6
15384080 2004
15
Spectrum of mutations in PTPN11 and genotype-phenotype correlation in 96 patients with Noonan syndrome and five patients with cardio-facio-cutaneous syndrome. 54 57 6 61
12634870 2003
16
Juvenile myelomonocytic leukaemia and Noonan syndrome. 6 57 61
25097206 2014
17
Germinal mosaicism in Noonan syndrome: A family with two affected siblings of normal parents. 57 6 61
20979190 2010
18
Noonan syndrome, the SOS1 gene and embryonal rhabdomyosarcoma. 6 25 54 61
20461756 2010
19
Prenatal detection of Noonan syndrome by mutation analysis of the PTPN11 and the KRAS genes. 61 54 6 25
20112233 2010
20
Tumor spectrum in children with Noonan syndrome and SOS1 or RAF1 mutations. 61 54 25 6
19953625 2010
21
SOS1 and PTPN11 mutations in five cases of Noonan syndrome with multiple giant cell lesions. 54 61 25 6
19352411 2009
22
Genomic duplication of PTPN11 is an uncommon cause of Noonan syndrome. 61 57 25 54
19760651 2009
23
Independent NF1 and PTPN11 mutations in a family with neurofibromatosis-Noonan syndrome. 57 6 61
19449407 2009
24
Craniosynostosis in patients with Noonan syndrome caused by germline KRAS mutations. 6 25 61 54
19396835 2009
25
PTPN11 analysis for the prenatal diagnosis of Noonan syndrome in fetuses with abnormal ultrasound findings. 25 6 61 54
18759865 2009
26
Clinical and molecular characterization of 40 patients with Noonan syndrome. 61 6 57
18678287 2008
27
Long-term GH treatment improves adult height in children with Noonan syndrome with and without mutations in protein tyrosine phosphatase, non-receptor-type 11. 25 6 54 61
18562489 2008
28
Duplication of chromosome band 12q24.11q24.23 results in apparent Noonan syndrome. 57 61 54 25
18348260 2008
29
Clinical manifestations in patients with SOS1 mutations range from Noonan syndrome to CFC syndrome. 6 25 54 61
18651097 2008
30
Mediating ERK 1/2 signaling rescues congenital heart defects in a mouse model of Noonan syndrome. 61 6 57
17641779 2007
31
Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy. 25 6 54 61
17603483 2007
32
Early fetal death associated with compound heterozygosity for Noonan syndrome-causative PTPN11 mutations. 57 61 6
17497712 2007
33
Expansion of the genotypic and phenotypic spectrum in patients with KRAS germline mutations. 61 25 54 6
17056636 2007
34
PTPN11 (Shp2) mutations in LEOPARD syndrome have dominant negative, not activating, effects. 61 6 57
16377799 2006
35
The mutational spectrum of PTPN11 in juvenile myelomonocytic leukemia and Noonan syndrome/myeloproliferative disease. 25 6 54 61
15928039 2005
36
Genotypic and phenotypic characterization of Noonan syndrome: new data and review of the literature. 57 61 6
15723289 2005
37
Activating mutations of the noonan syndrome-associated SHP2/PTPN11 gene in human solid tumors and adult acute myelogenous leukemia. 6 25 54 61
15604238 2004
38
Paternal germline origin and sex-ratio distortion in transmission of PTPN11 mutations in Noonan syndrome. 61 25 54 6
15248152 2004
39
Genetic evidence for lineage-related and differentiation stage-related contribution of somatic PTPN11 mutations to leukemogenesis in childhood acute leukemia. 61 25 6 54
14982869 2004
40
Noonan syndrome-associated SHP2/PTPN11 mutants cause EGF-dependent prolonged GAB1 binding and sustained ERK2/MAPK1 activation. 61 54 25 6
14974085 2004
41
Genetics and variation in phenotype in Noonan syndrome. 61 6 25 54
15539800 2004
42
Noonan syndrome with leukaemoid reaction and overproduction of catecholamines: a case report. 61 57 6
12739139 2003
43
PTPN11 mutation in a large family with Noonan syndrome and dizygous twinning. 61 6 57
12529711 2003
44
Juvenile myelomonocytic leukemia and Noonan syndrome. 57 6 61
10598665 1999
45
Oligo-astrocytoma in LZTR1-related Noonan syndrome. 61 6 25
30664951 2020
46
Delineation of LZTR1 mutation-positive patients with Noonan syndrome and identification of LZTR1 binding to RAF1-PPP1CB complexes. 6 25 61
30368668 2019
47
Mutations in LZTR1 drive human disease by dysregulating RAS ubiquitination. 61 6 25
30442762 2018
48
Autosomal recessive Noonan syndrome associated with biallelic LZTR1 variants. 61 6 25
29469822 2018
49
Spectrum of mutations and genotype-phenotype analysis in Noonan syndrome patients with RIT1 mutations. 61 6 25
26714497 2016
50
Recent advances in RASopathies. 6 25 61
26446362 2016

Variations for Noonan Syndrome 1

ClinVar genetic disease variations for Noonan Syndrome 1:

6 (show top 50) (show all 1542)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 RAF1 NM_001354689.3(RAF1):c.781C>A (p.Pro261Thr) SNV Pathogenic 40604 rs121434594 GRCh37: 3:12645688-12645688
GRCh38: 3:12604189-12604189
2 BRAF NM_001374258.1(BRAF):c.722C>A (p.Thr241Lys) SNV Pathogenic 44829 rs387906660 GRCh37: 7:140501350-140501350
GRCh38: 7:140801550-140801550
3 KRAS NM_033360.4(KRAS):c.*9T>G SNV Pathogenic 12591 rs104894367 GRCh37: 12:25362841-25362841
GRCh38: 12:25209907-25209907
4 BRAF NM_004333.6(BRAF):c.722C>G (p.Thr241Arg) SNV Pathogenic 29806 rs387906660 GRCh37: 7:140501350-140501350
GRCh38: 7:140801550-140801550
5 BRAF NM_004333.6(BRAF):c.1593G>C (p.Trp531Cys) SNV Pathogenic 29808 rs606231228 GRCh37: 7:140476813-140476813
GRCh38: 7:140777013-140777013
6 KRAS NM_004985.5(KRAS):c.214A>T (p.Met72Leu) SNV Pathogenic 179141 rs727504662 GRCh37: 12:25380244-25380244
GRCh38: 12:25227310-25227310
7 LZTR1 NM_006767.4(LZTR1):c.740G>A (p.Ser247Asn) SNV Pathogenic 209090 rs797045166 GRCh37: 22:21344763-21344763
GRCh38: 22:20990474-20990474
8 SOS2 NM_006939.4(SOS2):c.1127C>G (p.Thr376Ser) SNV Pathogenic 209091 rs869320687 GRCh37: 14:50628269-50628269
GRCh38: 14:50161551-50161551
9 RIT1 NM_006912.6(RIT1):c.244T>A (p.Phe82Ile) SNV Pathogenic 183406 rs869025194 GRCh37: 1:155874287-155874287
GRCh38: 1:155904496-155904496
10 RIT1 NM_006912.6(RIT1):c.241G>C (p.Glu81Gln) SNV Pathogenic 183404 rs869025192 GRCh37: 1:155874290-155874290
GRCh38: 1:155904499-155904499
11 BRAF NM_004333.6(BRAF):c.722C>G (p.Thr241Arg) SNV Pathogenic 29806 rs387906660 GRCh37: 7:140501350-140501350
GRCh38: 7:140801550-140801550
12 BRAF NM_004333.6(BRAF):c.1593G>C (p.Trp531Cys) SNV Pathogenic 29808 rs606231228 GRCh37: 7:140476813-140476813
GRCh38: 7:140777013-140777013
13 NRAS NM_002524.5(NRAS):c.101C>T (p.Pro34Leu) SNV Pathogenic 39647 rs397514553 GRCh37: 1:115258681-115258681
GRCh38: 1:114716060-114716060
14 RIT1 NM_006912.6(RIT1):c.229G>C (p.Ala77Pro) SNV Pathogenic 228289 rs869025191 GRCh37: 1:155874530-155874530
GRCh38: 1:155904739-155904739
15 KRAS NM_033360.4(KRAS):c.440A>G (p.Lys147Arg) SNV Pathogenic 431103 rs1135401776 GRCh37: 12:25378558-25378558
GRCh38: 12:25225624-25225624
16 BRAF NM_001374258.1(BRAF):c.721A>C (p.Thr241Pro) SNV Pathogenic 29807 rs387906661 GRCh37: 7:140501351-140501351
GRCh38: 7:140801551-140801551
17 LZTR1 NM_006767.4(LZTR1):c.2178C>A (p.Tyr726Ter) SNV Pathogenic 522799 rs1034395178 GRCh37: 22:21350360-21350360
GRCh38: 22:20996071-20996071
18 LZTR1 NM_006767.4(LZTR1):c.2220-17C>A SNV Pathogenic 599029 rs1249726034 GRCh37: 22:21350968-21350968
GRCh38: 22:20996679-20996679
19 LZTR1 NM_006767.4(LZTR1):c.2264G>A (p.Arg755Gln) SNV Pathogenic 599032 rs762834512 GRCh37: 22:21351029-21351029
GRCh38: 22:20996740-20996740
20 LZTR1 NM_006767.4(LZTR1):c.361C>G (p.His121Asp) SNV Pathogenic 599033 rs1569154492 GRCh37: 22:21341833-21341833
GRCh38: 22:20987544-20987544
21 LZTR1 NM_006767.4(LZTR1):c.1311G>A (p.Trp437Ter) SNV Pathogenic 549751 rs770933647 GRCh37: 22:21348001-21348001
GRCh38: 22:20993712-20993712
22 LZTR1 NM_006767.4(LZTR1):c.-38T>A SNV Pathogenic 549752 rs1459786357 GRCh37: 22:21336623-21336623
GRCh38: 22:20982334-20982334
23 LZTR1 NM_006767.4(LZTR1):c.1407G>A (p.Trp469Ter) SNV Pathogenic 549753 rs777243508 GRCh37: 22:21348266-21348266
GRCh38: 22:20993977-20993977
24 BRAF NM_001374258.1(BRAF):c.1712G>C (p.Trp571Ser) SNV Pathogenic 666569 rs397507478 GRCh37: 7:140476814-140476814
GRCh38: 7:140777014-140777014
25 BRAF NM_001374258.1(BRAF):c.1621G>A (p.Glu541Lys) SNV Pathogenic 13977 rs180177038 GRCh37: 7:140477807-140477807
GRCh38: 7:140778007-140778007
26 RRAS2 NM_012250.6(RRAS2):c.65_73dup (p.Gly22_Gly24dup) Duplication Pathogenic 626910 rs1591495776 GRCh37: 11:14380343-14380344
GRCh38: 11:14358797-14358798
27 RRAS2 NM_012250.6(RRAS2):c.68G>T (p.Gly23Val) SNV Pathogenic 626911 rs1591495779 GRCh37: 11:14380349-14380349
GRCh38: 11:14358803-14358803
28 RRAS2 NM_012250.6(RRAS2):c.208G>A (p.Ala70Thr) SNV Pathogenic 626912 rs782457908 GRCh37: 11:14316397-14316397
GRCh38: 11:14294851-14294851
29 SOS1 NM_005633.3(SOS1):c.1867T>A (p.Phe623Ile) SNV Pathogenic 636262 rs727505093 GRCh37: 2:39241979-39241979
GRCh38: 2:39014838-39014838
30 RIT1 NM_006912.6(RIT1):c.245T>C (p.Phe82Ser) SNV Pathogenic 694696 rs868208063 GRCh37: 1:155874286-155874286
GRCh38: 1:155904495-155904495
31 RIT1 NM_006912.6(RIT1):c.91G>C (p.Gly31Arg) SNV Pathogenic 694723 rs1571999498 GRCh37: 1:155880462-155880462
GRCh38: 1:155910671-155910671
32 GJB2 NM_004004.6(GJB2):c.205T>C (p.Phe69Leu) SNV Pathogenic 804361 rs1593351503 GRCh37: 13:20763516-20763516
GRCh38: 13:20189377-20189377
33 RIT1 NM_006912.6(RIT1):c.230C>G (p.Ala77Gly) SNV Pathogenic 850519 GRCh37: 1:155874529-155874529
GRCh38: 1:155904738-155904738
34 SOS1 NM_005633.4(SOS1):c.3134C>G (p.Pro1045Arg) SNV Pathogenic 932923 GRCh37: 2:39222476-39222476
GRCh38: 2:38995335-38995335
35 LZTR1 NM_006767.4(LZTR1):c.993+1G>A SNV Pathogenic 973830 GRCh37: 22:21346119-21346119
GRCh38: 22:20991830-20991830
36 SOS2 NM_006939.4(SOS2):c.791C>G (p.Thr264Arg) SNV Pathogenic 974590 GRCh37: 14:50649248-50649248
GRCh38: 14:50182530-50182530
37 LZTR1 NM_006767.4(LZTR1):c.1785+1G>C SNV Pathogenic 984443 GRCh37: 22:21349017-21349017
GRCh38: 22:20994728-20994728
38 CLTC NM_004859.4(CLTC):c.1912_1916delinsAGA (p.Ala639fs) Indel Pathogenic 984634 GRCh37: 17:57743970-57743974
GRCh38: 17:59666609-59666613
39 NRAS NM_002524.5(NRAS):c.149C>T (p.Thr50Ile) SNV Pathogenic 13902 rs267606921 GRCh37: 1:115256562-115256562
GRCh38: 1:114713941-114713941
40 SOS1 NM_005633.3(SOS1):c.1300G>A (p.Gly434Arg) SNV Pathogenic 40672 rs397517148 GRCh37: 2:39250269-39250269
GRCh38: 2:39023128-39023128
41 NRAS NM_002524.5(NRAS):c.149C>T (p.Thr50Ile) SNV Pathogenic 13902 rs267606921 GRCh37: 1:115256562-115256562
GRCh38: 1:114713941-114713941
42 NRAS NM_002524.5(NRAS):c.149C>T (p.Thr50Ile) SNV Pathogenic 13902 rs267606921 GRCh37: 1:115256562-115256562
GRCh38: 1:114713941-114713941
43 LZTR1 NM_006767.4(LZTR1):c.1084C>T (p.Arg362Ter) SNV Pathogenic 289969 rs189150283 GRCh37: 22:21346593-21346593
GRCh38: 22:20992304-20992304
44 SOS1 NM_005633.3(SOS1):c.1300G>A (p.Gly434Arg) SNV Pathogenic 40672 rs397517148 GRCh37: 2:39250269-39250269
GRCh38: 2:39023128-39023128
45 BRAF NM_001374258.1(BRAF):c.1575G>T (p.Leu525Phe) SNV Pathogenic 177844 rs180177036 GRCh37: 7:140477853-140477853
GRCh38: 7:140778053-140778053
46 SOS1 NM_005633.3(SOS1):c.1300G>A (p.Gly434Arg) SNV Pathogenic 40672 rs397517148 GRCh37: 2:39250269-39250269
GRCh38: 2:39023128-39023128
47 KRAS NM_004985.5(KRAS):c.173C>T (p.Thr58Ile) SNV Pathogenic 12588 rs104894364 GRCh37: 12:25380285-25380285
GRCh38: 12:25227351-25227351
48 KRAS NM_004985.5(KRAS):c.13A>G (p.Lys5Glu) SNV Pathogenic 12596 rs193929331 GRCh37: 12:25398306-25398306
GRCh38: 12:25245372-25245372
49 KRAS NM_033360.4(KRAS):c.178G>A (p.Gly60Ser) SNV Pathogenic 12597 rs104894359 GRCh37: 12:25380280-25380280
GRCh38: 12:25227346-25227346
50 SOS1 NM_005633.3(SOS1):c.797C>A (p.Thr266Lys) SNV Pathogenic 12869 rs137852812 GRCh37: 2:39278352-39278352
GRCh38: 2:39051211-39051211

UniProtKB/Swiss-Prot genetic disease variations for Noonan Syndrome 1:

72 (show all 39)
# Symbol AA change Variation ID SNP ID
1 PTPN11 p.Thr42Ala VAR_015601 rs397507501
2 PTPN11 p.Gly60Ala VAR_015602 rs397507509
3 PTPN11 p.Asp61Gly VAR_015603 rs121918461
4 PTPN11 p.Asp61Asn VAR_015604 rs397507510
5 PTPN11 p.Tyr62Asp VAR_015605 rs121918460
6 PTPN11 p.Tyr63Cys VAR_015606 rs121918459
7 PTPN11 p.Ala72Gly VAR_015607 rs121918454
8 PTPN11 p.Ala72Ser VAR_015608 rs121918453
9 PTPN11 p.Thr73Ile VAR_015609 rs121918462
10 PTPN11 p.Glu76Asp VAR_015610 rs397507514
11 PTPN11 p.Gln79Arg VAR_015611 rs121918466
12 PTPN11 p.Asp106Ala VAR_015612 rs397507517
13 PTPN11 p.Glu139Asp VAR_015613 rs397507520
14 PTPN11 p.Tyr279Cys VAR_015614 rs121918456
15 PTPN11 p.Ile282Val VAR_015615 rs397507529
16 PTPN11 p.Phe285Ser VAR_015616 rs121918463
17 PTPN11 p.Phe285Leu VAR_015617 rs397507531
18 PTPN11 p.Asn308Ser VAR_015618 rs121918455
19 PTPN11 p.Asn308Asp VAR_015619 rs28933386
20 PTPN11 p.Arg501Lys VAR_015622 rs397507543
21 PTPN11 p.Ser502Thr VAR_015623 rs121918458
22 PTPN11 p.Met504Val VAR_015624 rs397507547
23 PTPN11 p.Phe71Leu VAR_015995 rs397507512
24 PTPN11 p.Gly503Arg VAR_016003 rs397507545
25 PTPN11 p.Thr2Ile VAR_027183 rs267606990
26 PTPN11 p.Asn58Lys VAR_027184 rs397507506
27 PTPN11 p.Glu69Gln VAR_027185 rs397507511
28 PTPN11 p.Gln79Pro VAR_027186
29 PTPN11 p.Gln256Arg VAR_027187 rs397507523
30 PTPN11 p.Thr411Met VAR_027189 rs121918467
31 PTPN11 p.Gln506Arg VAR_027195
32 PTPN11 p.Thr59Ala VAR_066060 rs886043790
33 PTPN11 p.Pro491Ser VAR_071706 rs397507539
34 PTPN11 p.Gln510Glu VAR_076499 rs397507549
35 PTPN11 p.Leu261Phe VAR_078101 rs397507525
36 PTPN11 p.Leu261His VAR_078102 rs765642157
37 PTPN11 p.Leu262Phe VAR_078103
38 PTPN11 p.Leu262Arg VAR_078104 rs397507526
39 PTPN11 p.Arg265Gln VAR_078105 rs376607329

Expression for Noonan Syndrome 1

Search GEO for disease gene expression data for Noonan Syndrome 1.

Pathways for Noonan Syndrome 1

Pathways related to Noonan Syndrome 1 according to KEGG:

36
# Name Kegg Source Accession
1 Ras signaling pathway hsa04014
2 MAPK signaling pathway hsa04010

Pathways related to Noonan Syndrome 1 according to GeneCards Suite gene sharing:

(show top 50) (show all 203)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
14.36 SOS2 SOS1 RIT1 RASA2 RAF1 PTPN11
2
Show member pathways
14.17 SOS1 RASA2 RAF1 PTPN11 NRAS MAP2K1
3
Show member pathways
14.01 SOS2 SOS1 RRAS2 RAF1 PPP1CB NRAS
4
Show member pathways
14 SOS2 SOS1 RRAS2 RAF1 NRAS MAP2K1
5
Show member pathways
13.92 SOS1 RASA2 RAF1 PTPN11 NRAS MAP2K1
6
Show member pathways
13.86 SOS2 SOS1 RRAS2 RAF1 NRAS MAP2K1
7
Show member pathways
13.83 SOS2 SOS1 RRAS2 RAF1 NRAS MAP2K1
8
Show member pathways
13.77 SOS2 SOS1 RRAS2 RAF1 PTPN11 NRAS
9
Show member pathways
13.73 SOS2 SOS1 RRAS2 RAF1 NRAS MAP2K1
10
Show member pathways
13.73 SOS2 SOS1 RASA2 RAF1 PTPN11 NRAS
11
Show member pathways
13.65 SOS2 SOS1 RRAS2 RASA2 RAF1 PPP1CB
12
Show member pathways
13.61 SOS1 RAF1 PTPN11 NRAS KRAS HRAS
13
Show member pathways
13.59 SOS1 RASA2 RAF1 PTPN11 NRAS MAP2K1
14
Show member pathways
13.54 SOS2 SOS1 RRAS2 RAF1 PPP1CB NRAS
15
Show member pathways
13.53 SOS2 SOS1 RRAS2 RAF1 NRAS KRAS
16
Show member pathways
13.52 SOS2 SOS1 RRAS2 RAF1 NRAS MAP2K1
17
Show member pathways
13.47 SOS2 SOS1 RRAS2 RASA2 RAF1 NRAS
18
Show member pathways
13.41 SOS2 SOS1 RAF1 NRAS MAP2K1 KRAS
19
Show member pathways
13.33 SOS2 SOS1 RRAS2 RAF1 PPP1CB NRAS
20
Show member pathways
13.3 SOS2 SOS1 RRAS2 RAF1 NRAS MAP2K1
21
Show member pathways
13.29 SOS2 SOS1 RAF1 NRAS MAP2K1 KRAS
22
Show member pathways
13.28 SOS2 SOS1 RRAS2 RAF1 NRAS MAP2K1
23
Show member pathways
13.22 SOS2 SOS1 RRAS2 RAF1 PPP1CB NRAS
24
Show member pathways
13.2 SOS2 SOS1 RAF1 NRAS MAP2K1 KRAS
25
Show member pathways
13.17 SOS2 SOS1 RRAS2 RAF1 NRAS MAP2K1
26
Show member pathways
13.16 SOS2 SOS1 RAF1 NRAS MAP2K1 KRAS
27
Show member pathways
13.16 SOS2 SOS1 RRAS2 RAF1 NRAS MAP2K1
28
Show member pathways
13.16 SOS2 SOS1 RRAS2 RAF1 PPP1CB NRAS
29
Show member pathways
13.14 RRAS2 RAF1 NRAS MAP2K1 KRAS HRAS
30
Show member pathways
13.14 SOS2 SOS1 RRAS2 RAF1 NRAS MAP2K1
31
Show member pathways
13.13 SOS2 SOS1 RAF1 PTPN11 NRAS MAP2K1
32 13.12 SOS2 SOS1 RAF1 NRAS MAP2K1 KRAS
33
Show member pathways
13.12 SOS2 SOS1 RAF1 PTPN11 PPP1CB NRAS
34
Show member pathways
13.1 SOS2 SOS1 RAF1 NRAS MAP2K1 KRAS
35
Show member pathways
13.07 RAF1 NRAS MAP2K1 KRAS HRAS BRAF
36
Show member pathways
13.07 SOS2 SOS1 RRAS2 RAF1 NRAS MAP2K1
37
Show member pathways
13.06 SOS2 SOS1 RAF1 PTPN11 MAP2K1 KRAS
38
Show member pathways
13.03 SOS2 SOS1 RAF1 NRAS MAP2K1 KRAS
39 13.02 SOS2 SOS1 RRAS2 RASA2 RAF1 NRAS
40
Show member pathways
12.98 SOS1 PTPN11 NRAS KRAS HRAS
41
Show member pathways
12.96 SOS2 SOS1 RAF1 PTPN11 NRAS MAP2K1
42
Show member pathways
12.95 SOS2 SOS1 RAF1 NRAS MAP2K1 KRAS
43
Show member pathways
12.93 SOS1 PTPN11 NRAS KRAS HRAS CBL
44
Show member pathways
12.93 SOS2 SOS1 RAF1 NRAS MAP2K1 KRAS
45
Show member pathways
12.93 SOS2 SOS1 RAF1 PPP1CB NRAS MAP2K1
46
Show member pathways
12.92 RRAS2 RAF1 NRAS MAP2K1 KRAS HRAS
47
Show member pathways
12.91 PPP1CB NRAS MAP2K1 KRAS HRAS
48
Show member pathways
12.9 SOS2 SOS1 RRAS2 RAF1 PPP1CB NRAS
49
Show member pathways
12.88 SOS2 SOS1 RAF1 MAP2K1 KRAS BRAF
50
Show member pathways
12.88 SOS2 SOS1 RAF1 PTPN11 NRAS MAP2K1

GO Terms for Noonan Syndrome 1

Cellular components related to Noonan Syndrome 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 plasma membrane GO:0005886 9.97 SOS1 RRAS2 RIT1 RAF1 PPP1CB NRAS
2 Golgi apparatus GO:0005794 9.8 RRAS2 RAF1 NRAS MAP2K1 LZTR1 HRAS
3 cytosol GO:0005829 9.8 SOS2 SOS1 SHOC2 RASA2 RAF1 PTPN11
4 protein phosphatase type 1 complex GO:0000164 9.32 SHOC2 PPP1CB
5 focal adhesion GO:0005925 9.1 RRAS2 PPP1CB MAP2K1 KRAS CLTC CBL

Biological processes related to Noonan Syndrome 1 according to GeneCards Suite gene sharing:

(show all 20)
# Name GO ID Score Top Affiliating Genes
1 signal transduction GO:0007165 9.93 SOS1 SHOC2 RRAS2 RIT1 RASA2 RAF1
2 positive regulation of ERK1 and ERK2 cascade GO:0070374 9.86 PTPN11 MAP2K1 HRAS BRAF
3 fibroblast growth factor receptor signaling pathway GO:0008543 9.76 SHOC2 PTPN11 CBL
4 stimulatory C-type lectin receptor signaling pathway GO:0002223 9.73 RAF1 NRAS KRAS HRAS
5 thymus development GO:0048538 9.67 RAF1 MAP2K1 BRAF
6 regulation of T cell proliferation GO:0042129 9.59 SOS2 SOS1
7 Bergmann glial cell differentiation GO:0060020 9.58 PTPN11 MAP2K1
8 thyroid gland development GO:0030878 9.58 RAF1 MAP2K1 BRAF
9 lymphocyte homeostasis GO:0002260 9.57 SOS2 SOS1
10 epidermal growth factor receptor signaling pathway GO:0007173 9.56 SOS1 PTPN11 CBL BRAF
11 MAPK cascade GO:0000165 9.56 SOS1 RASA2 RAF1 NRAS MAP2K1 KRAS
12 response to isolation stress GO:0035900 9.55 KRAS HRAS
13 positive regulation of small GTPase mediated signal transduction GO:0051057 9.54 SOS2 SOS1
14 neurotrophin TRK receptor signaling pathway GO:0048011 9.54 SOS1 RAF1 PTPN11
15 regulation of axon regeneration GO:0048679 9.52 MAP2K1 BRAF
16 regulation of T cell differentiation in thymus GO:0033081 9.51 SOS2 SOS1
17 face development GO:0060324 9.5 RAF1 MAP2K1 BRAF
18 regulation of pro-B cell differentiation GO:2000973 9.48 SOS2 SOS1
19 cerebellar cortex formation GO:0021697 9.46 PTPN11 MAP2K1
20 Ras protein signal transduction GO:0007265 9.17 SOS1 SHOC2 RRAS2 RIT1 NRAS KRAS

Molecular functions related to Noonan Syndrome 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nucleotide binding GO:0000166 9.92 RRAS2 RIT1 RAF1 NRAS MAP2K1 KRAS
2 protein-containing complex binding GO:0044877 9.65 RAF1 NRAS KRAS HRAS BRAF
3 GTP binding GO:0005525 9.55 RRAS2 RIT1 NRAS KRAS HRAS
4 mitogen-activated protein kinase kinase binding GO:0031434 9.37 RAF1 BRAF
5 GTPase activity GO:0003924 9.35 RRAS2 RIT1 NRAS KRAS HRAS
6 GDP binding GO:0019003 9.02 RRAS2 RIT1 NRAS KRAS HRAS

Sources for Noonan Syndrome 1

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
Content
Loading form....